Monoclonal Antibodies

Cancer cells express a variety of antigens that are attractive targets for monoclonal antibody-based therapy (Table 51-3). Several monoclonal antibodies are FDA-approved for treating lymphoid and solid tumor malignancies, including rituximab and alemtuz,umab for lymphoid malignancies, and trastuzumab for breast cancer. Because murine monoclonal antibodies have a short t1/2 and induce a human anti-mouse antibody immune response, they usually are chimerized or humanized when used as therapeutic agents. The nomenclature adopted for therapeutic monoclonal antibodies is to terminate the name in -ximab for chimeric antibodies and -umab for humanized antibodies. A variety of mechanism(s) of cell killing have been described for naked monoclonal antibodies, including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and direct induction of apoptosis, but the clinically relevant mechanisms remain uncertain. Monoclonal antibodies also may be engineered to combine the antibody with a toxin (immunotoxins), such as gemtuzumab ozogamicin (mylotarg) or denileukin diftitox (ontak), or combined with a radioactive isotope, as in the case of 90Y-ibritumomab tiuxetan (zevalin) (Table 51-3). More recently, antibodies have been engineered to contain a second specificity, known as bi-specific antibodies.

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